TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans
TRPA1 Channel Activation With Cinnamaldehyde Induces Cutaneous Vasodilation Through NOS, but Not COX and KCa Channel, Mechanisms in Humans
复制标题
肉桂醛激活 TRPA1 通道可通过 NOS（而非 COX 和 KCa 通道）诱导皮肤血管舒张，这是人类的机制
DOI：
10.1097/fjc.0000000000001188
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发表时间：
2022
影响因子：
3
通讯作者：
Fujii Naoto
中科院分区：
文献类型：
--
作者：
Kataoka Yufuko;Kenny Glen P.;Nishiyasu Takeshi;Amano Tatsuro;M?ndel Toby;Zheng Huixin;Lei Tze-Huan;Watanabe Koichi;Fujii Naoto
瞬时受体电位锚蛋白1（TRPA 1）通道激活诱导人体内皮肤血管舒张。然而，这种反应的机制仍然不明确。我们假设一氧化氮合酶（NOS）和钙激活的钾离子（KCa）通道参与了TRPA 1通道诱导的皮肤血管舒张作用，而不涉及环氧化酶（考克斯）。用1.985%二甲基亚砜+0.015%乳酸林格液-丙二醇皮内微透析法测定了9名健康青年前臂背侧4个部位的皮肤血管传导性（CVC）（载体对照），（2）10 mM l-NAME，一种非选择性NOS抑制剂，（3）10 mM酮咯酸，一种非选择性考克斯抑制剂，或（4）50 mM四乙基铵，一种非选择性KCa通道阻断剂。以剂量依赖性方式（2.9%、8.8%、26%和80%，每次持续≥ 30分钟）向每个皮肤部位给予肉桂醛（一种TRPA 1通道激活剂）。给予≥ 8.8%肉桂醛使溶剂对照部位的CVC较基线增加了27.4%（95%置信区间为5.3; P< 0.001）。NOS抑制剂在相对于媒介物对照部位的8.8%、26%和80%浓度下减弱肉桂醛诱导的CVC增加（所有P≤ 0.05）。相比之下，对于所有浓度，考克斯抑制剂和KCa通道阻滞剂均未减弱肉桂醛诱导的CVC相对于溶媒对照部位的增加（所有P均≥ 0.130）。我们的结论是，在人体皮肤在体内，NOS起着调节皮肤血管舒张反应TRPA 1通道激活的作用，没有检测到的贡献考克斯和KCa通道。
Transient receptor potential ankyrin 1 (TRPA1) channel activation induces cutaneous vasodilation in humans in vivo. However, the mechanisms underlying this response remains equivocal. We hypothesized that nitric oxide synthase (NOS) and Ca 2+ activated K+(KCa) channels contribute to the TRPA1 channel–induced cutaneous vasodilation with no involvement of cyclooxygenase (COX). Cutaneous vascular conductance (CVC) in 9 healthy young adults was assessed at 4 dorsal forearm skin sites treated by intradermal microdialysis with (1) 1.985% dimethyl sulfoxide+ 0.015% lactated Ringer solution with propylene glycol (vehicle control),(2) 10 mM l-NAME, a nonselective NOS inhibitor,(3) 10 mM ketorolac, a nonselective COX inhibitor, or (4) 50 mM tetraethylammonium, a nonselective KCa channel blocker. Cinnamaldehyde, a TRPA1 channel activator, was administered to each skin site in a dose-dependent manner (2.9%, 8.8%, 26%, and 80%, each lasting≥ 30 minutes). Administration of≥ 8.8% cinnamaldehyde increased CVC from baseline at the vehicle control site by as much as 27.4%(95% confidence interval of 5.3; P< 0.001). NOS inhibitor attenuated the cinnamaldehyde-induced increases in CVC at the 8.8%, 26%, and 80% concentrations relative to the vehicle control site (all P≤ 0.05). In contrast, both the COX inhibitor and KCa channel blockers did not attenuate the cinnamaldehyde induced-increases in CVC relative to the vehicle control site for all concentrations (all P≥ 0.130). We conclude that in human skin in vivo, NOS plays a role in modulating the regulation of cutaneous vasodilation in response to TRPA1 channel activation with no detectable contributions of COX and KCa channels.